A Population Model of Time-Dependent Changes in Serum Creatinine in (Near)term Neonates with Hypoxic-Ischemic Encephalopathy During and After Therapeutic Hypothermia.

Autor: Krzyzanski W; Department of Pharmaceutical Sciences, University at Buffalo, 370 Pharmacy Building, Buffalo, New York, 14214, USA., Wintermark P; Division of Newborn Medicine, Department of Pediatrics, McGill University, Montreal Children's Hospital, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada., Annaert P; Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Louvain, Belgium., Groenendaal F; Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, and Utrecht University, Utrecht, The Netherlands.; Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands., Şahin S; Department of Neonatology, Faculty of Medicine, Izmir Demokrasi University, Izmir, Turkey., Öncel MY; Department of Neonatology, Faculty of Medicine, İzmir Katip Çelebi University, İzmir, Turkey., Armangil D; Neonatal Intensive Care Unit, Koru Hospital, Ankara, Turkey., Koc E; Department of Neonatology, Faculty of Medicine, Gazi University, Ankara, Turkey., Battin MR; Newborn Service, Auckland District Health Board, Auckland, New Zealand., Gunn AJ; Department of Physiology, University of Auckland, Auckland, New Zealand., Frymoyer A; Neonatal and Developmental Medicine, Stanford University School of Medicine, Palo Alto, California, USA., Chock VY; Neonatal and Developmental Medicine, Stanford University School of Medicine, Palo Alto, California, USA., Keles E; Department of Neonatology, Faculty of Medicine, Gazi University, Ankara, Turkey., Mekahli D; Department of Pediatric Nephrology, University Hospitals, Louvain, Belgium.; PKD Research Group, Department of Cellular and Molecular Medicine, KU Leuven, Louvain, Belgium., van den Anker J; Division of Clinical Pharmacology, Children's National Hospital, Washington, District of Columbia, USA.; Division of Paediatric Pharmacology and Pharmacometrics, University Children's Hospital Basel, University of Basel, Basel, Switzerland., Smits A; Department of Development and Regeneration, KU Leuven, Louvain, Belgium.; Neonatal Intensive Care Unit, University Hospitals Leuven, Louvain, Belgium., Allegaert K; Department of Pharmaceutical Sciences, University at Buffalo, 370 Pharmacy Building, Buffalo, New York, 14214, USA. k.allegaert@erasmusmc.nl.; Division of Paediatric Pharmacology and Pharmacometrics, University Children's Hospital Basel, University of Basel, Basel, Switzerland. k.allegaert@erasmusmc.nl.; Department of Development and Regeneration, KU Leuven, Louvain, Belgium. k.allegaert@erasmusmc.nl.; Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000, Louvain, Belgium. k.allegaert@erasmusmc.nl.; Department of Hospital Pharmacy, Erasmus MC University Medical Center, 3015, Rotterdam, The Netherlands. k.allegaert@erasmusmc.nl.
Jazyk: angličtina
Zdroj: The AAPS journal [AAPS J] 2023 Dec 05; Vol. 26 (1), pp. 4. Date of Electronic Publication: 2023 Dec 05.
DOI: 10.1208/s12248-023-00851-0
Abstrakt: The objective was to apply a population model to describe the time course and variability of serum creatinine (sCr) in (near)term neonates with moderate to severe encephalopathy during and after therapeutic hypothermia (TH). The data consisted of sCr observations up to 10 days of postnatal age in neonates who underwent TH during the first 3 days after birth. Available covariates were birth weight (BWT), gestational age (GA), survival, and acute kidney injury (AKI). A previously published population model of sCr kinetics in neonates served as the base model. This model predicted not only sCr but also the glomerular filtration rate normalized by its value at birth (GFR/GFR 0 ). The model was used to compare the TH neonates with a reference full term non-asphyxiated population of neonates. The estimates of the model parameters had good precision and showed high between subject variability. AKI influenced most of the estimated parameters denoting a strong impact on sCr kinetics and GFR. BWT and GA were not significant covariates. TH transiently increased [Formula: see text] in TH neonates over the first days compared to the reference group. Asphyxia impacted not only GFR, but also the [Formula: see text] synthesis rate. We also observed that AKI neonates exhibit a delayed onset of postnatal GFR increase and have a higher [Formula: see text] synthesis rate compared to no-AKI patients. Our findings show that the use of [Formula: see text] as marker of renal function in asphyxiated neonates treated with TH to guide dose selection for renally cleared drugs is challenging, while we captured the postnatal sCr patterns in this specific population.
(© 2023. The Author(s).)
Databáze: MEDLINE
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